The change in B-type natriuretic peptide levels over time predicts significant rejection in cardiac transplant recipients

J Heart Lung Transplant. 2009 Jul;28(7):704-9. doi: 10.1016/j.healun.2009.04.019.


Background: B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection.

Methods: N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations.

Results: A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters.

Conclusions: There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.

MeSH terms

  • Biomarkers / metabolism
  • Biopsy
  • Cross-Sectional Studies
  • Female
  • Graft Rejection / diagnosis*
  • Graft Rejection / metabolism*
  • Graft Rejection / pathology
  • Heart Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Myocardium / metabolism
  • Myocardium / pathology
  • Natriuretic Peptide, Brain / metabolism*
  • Peptide Fragments / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Sensitivity and Specificity


  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain